Reversine induces autophagic cell death through the AMP-activated protein kinase pathway in urothelial carcinoma cells.

Urothelial carcinoma is one of the most common malignancies of the urinary tract. Effective treatment of advanced urothelial carcinoma remains a clinical challenge with poor outcomes in these patients. Previous reports have shown that the expression of aurora kinase is associated with clinical stage and prognosis; hence, aurora kinases are potential targets in urothelial carcinoma therapy. Reversine, an aurora kinase inhibitor, was analyzed for its cytotoxicity in this study. Cell proliferation, flow cytometry, western blotting, and immunofluorescent assay were used to determine the effect of reversine on urothelial carcinoma cells. The results showed that reversine significantly inhibits the growth of urothelial carcinoma cell lines. Reversine induced cell cycle arrest at the G2/M phase, leading to autophagic cell death by activating the AMP-activated protein kinase pathway. Reversine induced significant cell death in urothelial carcinoma cells. Our results suggest that reversine may be a suitably small molecule for treating urothelial carcinoma in the future.

Chronic Kidney Disease is Associated With Upper Tract Urothelial Carcinoma: A Nationwide Population-Based Cohort Study in Taiwan.

Increased urinary tract malignancy has been reported in end-stage renal disease (ESRD). However, little is known about chronic kidney disease (CKD). This study is designed to explore the association between CKD and upper tract urothelial carcinoma (UTUC).Using Taiwan's Longitudinal Health Insurance Database, we studied CKD patients between January 2000 and December 2011. The non-CKD controls were selected at a ratio of 4:1 and frequency matched by gender, age group, and index date. We used the chi-square test and t test to analyze the sociodemographic information and comorbidities. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI).The selected cases included 45,321 CKD cases and 181,284 controls. A significantly higher incidence of UTUC was noted in the CKD group (0.22% vs 0.07%, P < 0.001). In univariate analysis, CKD, female gender, age, hypertension, hematuria, repeated urinary tract infection, bladder cancer, and ESRD were all associated with UTUC. In multivariate analysis, only CKD, female gender, age, hematuria, bladder cancer, and ESRD were significantly associated. The HR for CKD was 1.63 (95% CI: 1.26-2.13). Females had a higher HR of 1.38 (95% CI: 1.11-1.71). After excluding those patients who progressed to dialysis or kidney transplantation, the risk for CKD was still high, with an HR of 1.72 (95% CI: 1.33-2.33).CKD is a significant factor associated with UTUC. We should pay attention to the possibility of UTUC for CKD patients before they progress to ESRD.

Acute Urinary Retention During Pregnancy--A Nationwide Population-Based Cohort Study in Taiwan.

The aim of the study was to investigate the epidemiology and risk factors of acute urinary retention (AUR) during pregnancy. We included all cases of pregnancies with AUR reported in Taiwan's Longitudinal Health Insurance Database from January 1, 1998, to December 31, 2011. Cases of AUR onset 1 day before delivery were excluded. The Cochrane-Armitage trend test and logistic regression analysis were used to evaluate the age distribution and types of deliveries of pregnant women. Chi-square tests and Fisher's exact test were performed to examine the association among all covariates. The odds ratios (OR) and 95% confidence intervals (CI) were estimated. We identified 308 cases of AUR in 65,490 pregnancies. The risk of AUR during pregnancy was 0.47%. The peak incidence occurred between the 9th and 16th gestational weeks. Patients who experienced preterm delivery exhibited the highest risk for AUR (2.18%). Those with post-term delivery had the second highest risk (0.46%), and patients with a normal delivery exhibited the lowest risk (0.33%). Compared with normal delivery, preterm delivery carried a higher risk of AUR (OR: 6.33, 95% CI: 4.94-8.11). The AUR risk was higher for patients with advanced maternal age (>35 years old) than it was for those in the younger group (< 20 years old) (OR: 2.62, 95% CI: 1.18-5.81). Within the normal delivery group, higher incidences of urogenital infection, gestational diabetes mellitus, previous abortion, abnormal pelvis, disproportion, and endometriosis were noted in women with AUR than in those without AUR (all P values <0.05). Women with advanced maternal age and those who experienced preterm delivery had an increased risk for AUR. The peak incidence of AUR in normal pregnancies occurred between the 9th and 16th gestational weeks. Urogenital infection, gestational diabetes mellitus, previous abortion, abnormal pelvis, disproportion, and endometriosis were associated with AUR in women who underwent a normal delivery.

Diurnal temperature change is associated with testicular torsion: a nationwide, population based study in Taiwan.

PURPOSE: We investigated the association between climatic variables and testicular torsion in Taiwanese males. MATERIALS AND METHODS: Using the Taiwan Longitudinal Health Insurance Database, we reviewed the files of patients who were diagnosed with testicular torsion and underwent orchiectomy or orchiopexy between January 1996 and December 2008. Children younger than 1 year were excluded from the study. Climatic data were provided by the Taiwan Central Weather Bureau and included ambient temperature, relative humidity, diurnal temperature change and barometric pressure. Patients with acute appendicitis who underwent appendectomy were chosen as the control group. Climatic variables in relation to testicular torsion were analyzed using the Mann-Whitney U test and chi-square test, and seasonal climatic variations using the Kruskal-Wallis H test. Relative risk was calculated to compare the incidence of testicular torsion for diurnal temperature changes. RESULTS: A total of 65 patients with a mean age of 16.2 years presented with testicular torsion and were treated surgically. Four children younger than 1 year were excluded, and thus the study population consisted of 61 patients. The estimated incidence of testicular torsion was 2.58 per 100,000 person-years. There were no special climatic conditions on days of admission. However, 73.7% of the patients had testicular torsion when the diurnal temperature change was 6C or greater. Compared to the torsion rate for diurnal temperature changes less than 6C, the relative risk of testicular torsion at 6C or greater was 1.8 (p = 0.05). Average seasonal diurnal temperature change in the 2 days before hospitalization showed increases in all seasons except spring, which fluctuated. CONCLUSIONS: Diurnal temperature change was associated with testicular torsion and may be an etiological climatic factor affecting this condition. This is the first known study to demonstrate an association between diurnal temperature change and testicular torsion.

Acute urinary retention increases the risk of complications after transurethral resection of the prostate: a population-based study.

UNLABELLED: Study Type--Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Higher mortality and morbidity rates in men presenting with AUR have been reported in previous studies. This study has comprehensive comparisons of post-TURP complications between patients with and without AUR. Furthermore, it shows that AUR is associated with increased risk of complications after TURP. OBJECTIVE: • To assess the association between a history of acute urinary retention (AUR) and complications after transurethral resection of prostate (TURP). PATIENTS AND METHODS: • We conducted a retrospective, national, population-based study using Taiwan's National Health Insurance Research Database. • We included men > 50 years old, diagnosed with benign prostatic hyperplasia (BPH) and divided these into two groups: an AUR(+) group--those with AUR who underwent TURP between 2002 and 2004; and an AUR(-) group--those without AUR who underwent TURP between those dates. • Prostate cancer, Parkinsonism and multiple sclerosis were exclusion criteria. • Postoperative complications, e.g. re-catheterization, haematuria or urinary tract infection (UTI), were compared using crude odds ratios (ORs), 95% confidence intervals (CIs), and Student's t-test. • A chi-squared test was used for potential confounding factors: preoperative UTI and anticoagulant use. • Univariate and multivariate analysis on medical expenses were conducted. RESULTS: • The AUR(+) group contained 3305 men; the AUR(-) group contained 1062. • Re-catheterization (13.8%), septicaemia (1.1%) and shock (0.3%) were found only in the AUR(+) group. • The AUR(+) group had more UTIs (18.9% vs. 15.6%, OR: 1.26, 95% CI: 1.05-1.52), more lower urinary tract symptoms (22.8% vs. 16.9%, OR: 1.45, 95% CI: 1.21-1.73), fewer blood transfusions (3.2% vs. 1.5%, OR: 2.19, 95% CI: 1.29-3.72) and higher medical expenses. • There were no significant differences in haematuria, lower urinary tract stricture, or re-surgical intervention of the prostate and second-line antibiotic use. CONCLUSION: • Patients in Taiwan with BPH with AUR who were treated by TURP were associated with a higher risk of complications, longer hospital stay and more comorbidities than those without AUR and a preoperative warning is warranted for these patients.